Drug Addiction: From Basic Research to Therapy

791 Pages·2008·6.24 MB·English

by  Per Svenningsson

Drug Addiction
From Basic Research to Therapy
Rao S. Rapaka • Wolfgang Sadée
Editors
Drug Addiction
From Basic Research to Therapy
Editors
Dr. Rao S. Rapaka Dr. Wolfgang Sadée
National Institute on Drug Abuse College of Medicine and Public Health
Bethesda, MD Ohio State University
USA Columbus, OH
USA
ISBN: 978-0-387-76677-5 e-ISBN: 978-0-387-76678-2
DOI: 10.1007/978-0-387-76678-2
Library of Congress Control Number: 2008926485
© 2008 American Association of Pharmaceutical Scientists
All rights reserved. This work may not be translated or copied in whole or in part without the written
permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY
10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in
connection with any form of information storage and retrieval, electronic adaptation, computer
software, or by similar or dissimilar methodology now known or hereafter developed is forbidden.
The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are
not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject
to proprietary rights.
Printed on acid-free paper
9 8 7 6 5 4 3 2 1
springer.com
Preface
This book affords a comprehensive overview of current research on drug addiction
and related disciplines, with topical reviews written by eminent scientists in the field.
It was inspired by a joint AAPS–NIDA symposium “Frontiers in Science: Drug
Addiction – From Basic Research to Therapies”, held in September 2004, at the NIH
campus. Subsequently, we have invited leading scientists to contribute chapters on a
broad range of topics, covering basic research (e.g. mechanisms of action of drugs of
abuse, development of receptor-specific ligands, animal models), discovery and
development of therapies, and other clinical applications. As neuronal circuits
involved in drug addiction also impinge upon many other vital functions of the brain
and peripheral tissues, we have broadened the scope to include pathophysiologies
related to drug abuse/addiction. For example, the complex actions of opioids on pain,
addiction liability, and other adverse effects have triggered an intensive search for
non-addictive opioid pain medications and for non-opioid analgesics directed against
novel targets. Other directions include treatment of stimulant addiction and toxicity,
new therapies for gastrointestinal dysfunction, inflammation, cognitive and neurode-
generative disorders, and immunological diseases.
This book is divided into several portions, each addressing issues of importance
in drug addiction or in scientific areas that have naturally evolved as research targets
for addiction researchers:
1. General topics
2. Transporters and stimulants and hallucinogens
3. Drug design: nicotine, opioids, and related ligands
4. Opioids: general
5. Cannabinoids
The first section starts out with a detailed analysis of a principal addiction path-
way involving DARPP32, a key regulator of dopamine signaling, presented by
Greengard and colleagues. This is followed by drug discovery from natural sources
(Kinghorn), antibodies, endogenous peptides, and small RNAs as drug candidates,
and computational analysis of G protein coupled receptors (Reggio). The scope of
basic topics further includes pharmacogenetics (Rutter), and addresses the role of
chemokines, nicotinic receptors, and PDZ domains as protein–protein interaction
modules.
v
vi Preface
The second section addresses issues related to neurotransmitter transporters and
their role in mediating the effects of stimulants and hallucinogens. This focuses
on monoamine synaptic reuptake transporters and cocaine, among other stimulants.
A series of chapters further discuss the interaction of stimulants and hallucinogens
with various receptors and their mechanisms of action.
The third section “Drug design: nicotine, opioids, and related ligands” critically
assesses the molecular biology, physiology, and pharmacology of receptors and
other targets for drugs of abuse. Focusing on drug design, several chapters address
the basic tools for drug discovery such as crystallography and chemistry, with appli-
cations to opioid and nicotinic receptors. This leads to Sect. 4 with opioid ligands
and their interaction with target receptors as the focus. Relevant issues include
molecular modes of target interactions, opioid receptor regulation and tolerance, the
relevance of receptor oligomerization, CNS drug delivery, homology modeling, and
the serendipitous discovery of cell-permeable, mitochondrial-targeted peptide anti-
oxidants – an example of a distinct application arising from addiction research.
The last section deals with cannabinoids, an area of tremendous recent growth
because of the role cannabinoids play in multiple physiological systems, including
those involved in pain modulation.
These diverse disciplines and technologies all converge on a more detailed
understanding of addiction and the promise for developing improved treatment
strategies for a spectrum of neurological disorders. This volume uniquely brings
together seemingly disparate, but nevertheless complementary critical reviews that
together paint a rather comprehensive picture of current efforts in drug addiction
and its treatment. It also shows how one discipline reaches into many other areas,
with the interplay among them yielding the promise for significant advances in
understanding and treating drug addiction and related disorders.
Columbus, OH Rao S. Rapaka
Wolfgang Sadee
Contents
I General Topics
1 DARPP-32 Mediates the Actions of Multiple Drugs of Abuse . . . . . . . . . 3
Per Svenningsson, Angus C. Nairn, and Paul Greengard
2 Drug Discovery From Natural Sources. . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Young-Won Chin, Marcy J. Balunas, Hee Byung Chai, and
A. Douglas Kinghorn
3 Computational Methods in Drug Design: Modeling G
Protein-Coupled Receptor Monomers, Dimers, and Oligomers. . . . . . . 41
Patricia H. Reggio
4 Symbiotic Relationship of Pharmacogenetics and Drugs
of Abuse. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Joni L. Rutter
5 Monoclonal Antibody Form and Function: Manufacturing
the Right Antibodies for Treating Drug Abuse. . . . . . . . . . . . . . . . . . . . . 87
Eric Peterson, S. Michael Owens, and Ralph L. Henry
6 Cocaine- and Amphetamine-Regulated Transcript Peptides
Play a Role in Drug Abuse and Are Potential
Therapeutic Targets. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Michael J. Kuhar, Jason N. Jaworski, George W. Hubert,
Kelly B. Philpot, and Geraldina Dominguez
7 RNAi-Directed Inhibition of DC-SIGN by Dendritic Cells:
Prospects for HIV-1 Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Madhavan P.N. Nair, Jessica L. Reynolds, Supriya D. Mahajan,
Stanley A. Schwartz, Ravikumar Aalinkeel, B. Bindukumar,
and Don Sykes
vii
viii Contents
8 Viewing Chemokines as a Third Major System of
Communication in the Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Martin W. Adler, Ellen B. Geller, Xiaohong Chen,
and Thomas J. Rogers
9 Targeting the PDZ Domains of Molecular Scaffolds
of Transmembrane Ion Channels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Andrea Piserchio, Mark Spaller, and Dale F. Mierke
10 Neuronal Nicotinic Acetylcholine Receptor Expression
and Function on Nonneuronal Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Lorise C. Gahring and Scott W. Rogers
II Transporters & Stimulants & Hallucinogens
11 Role of Monoamine Transporters in Mediating
Psychostimulant Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Evan L. Riddle, Annette E. Fleckenstein, and Glen R. Hanson
12 Development of the Dopamine Transporter Selective RTI-336
as a Pharmacotherapy for Cocaine Abuse . . . . . . . . . . . . . . . . . . . . . . 179
F. Ivy Carroll, James L. Howard, Leonard L. Howell,
Barbara S. Fox, and Michael J. Kuhar
13 Serotonin Transporters: Implications for Antidepressant
Drug Development. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Kellie J. White, Crystal C. Walline, and Eric L. Barker
14 Recent Advances for the Treatment of Cocaine Abuse:
Central Nervous System Immunopharmacotherapy. . . . . . . . . . . . . . 217
Tobin J. Dickerson and Kim D. Janda
15 k Opioids as Potential Treatments for Stimulant Dependence . . . . . . 231
Thomas E. Prisinzano, Kevin Tidgewell, and Wayne W. Harding
16 Regulation of Monoamine Transporters: Influence of
Psychostimulants and Therapeutic Antidepressants . . . . . . . . . . . . . . 247
Lankupalle D. Jayanthi and Sammanda Ramamoorthy
17 Hallucinogen Actions on 5-HT Receptors Reveal Distinct
Mechanisms of Activation and Signaling by
G Protein-Coupled Receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
Harel Weinstein
Contents ix
18 Recognition of Psychostimulants, Antidepressants, and Other
Inhibitors of Synaptic Neurotransmitter Uptake by the Plasma
Membrane Monoamine Transporters . . . . . . . . . . . . . . . . . . . . . . . . . . 287
Christopher K. Surratt, Okechukwu T. Ukairo, and
Suneetha Ramanujapuram
19 Dual Dopamine/Serotonin Releasers as Potential Medications
for Stimulant and Alcohol Addictions. . . . . . . . . . . . . . . . . . . . . . . . . . 311
Richard B. Rothman, Bruce E. Blough, and Michael H. Baumann
20 Receptors of Mammalian Trace Amines. . . . . . . . . . . . . . . . . . . . . . . . 327
Anita H. Lewin
III Drug Design: Nicotine, Opioids and Related Ligands
21 The Role of Crystallography in Drug Design. . . . . . . . . . . . . . . . . . . . 343
Jeffrey R. Deschamps
22 Opioid Peptide-Derived Analgesics . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357
Peter W. Schiller
23 Opioid Ligands with Mixed µ/d Opioid Receptor Interactions:
An Emerging Approach to Novel Analgesics . . . . . . . . . . . . . . . . . . . . 367
Subramaniam Ananthan
24 Small-Molecule Agonists and Antagonists of the Opioid
Receptor-Like Receptor (ORL1, NOP): Ligand-Based Analysis
of Structural Factors Influencing Intrinsic Activity at NOP . . . . . . . 381
Nurulain Zaveri, Faming Jiang, Cris Olsen, Willma Polgar,
and Lawrence Toll
25 Kappa Opioid Antagonists: Past Successes
and Future Prospects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395
Matthew D. Metcalf and Andrew Coop
26 In Vitro and Direct In Vivo Testing of Mixture-Based
Combinatorial Libraries for the Identification of Highly Active
and Specific Opiate Ligands. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433
Richard A. Houghten, Colette T. Dooley, and Jon R. Appel
27 Current Status of Immunologic Approaches to Treating Tobacco
Dependence: Vaccines and Nicotine-Specific Antibodies. . . . . . . . . . . 455
Mark G. LeSage, Daniel E. Keyler, and Paul R. Pentel
x Contents
28 New Paradigms and Tools in Drug Design
for Pain and Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
Victor J. Hruby, Frank Porreca, Henry I. Yamamura, Gordon Tollin,
Richard S. Agnes, Yeon Sun Lee, Minying Cai, Isabel Alves,
Scott Cowell, Eva Varga, Peg Davis, Zdzislaw Salamon,
William Roeske, Todd Vanderah, and Josephine Lai
IV Opioids: General
29 Neuropeptide-Processing Enzymes: Applications
for Drug Discovery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497
Lloyd D. Fricker
30 CNS Drug Delivery: Opioid Peptides
and the Blood-Brain Barrier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 511
Ken A. Witt and Thomas P. Davis
31 Cell-Permeable, Mitochondrial-Targeted, Peptide Antioxidants . . . . 535
Hazel H. Szeto
32 Targeting Opioid Receptor Heterodimers: Strategies
for Screening and Drug Development . . . . . . . . . . . . . . . . . . . . . . . . . . 547
Achla Gupta, Fabien M. Décaillot, and Lakshmi A. Devi
33 Homology Modeling of Opioid Receptor-Ligand Complexes
Using Experimental Constraints . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
Irina D. Pogozheva, Magdalena J. Przydzial, and Henry I. Mosberg
34 Molecular Recognition of Opioid Receptor Ligands . . . . . . . . . . . . . . 585
Brian E. Kane, Bengt Svensson, and David M. Ferguson
35 Role of Morphine’s Metabolites in Analgesia: Concepts
and Controversies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609
Erica Wittwer and Steven E. Kern
36 Mu Opioid Receptor Regulation and Opiate Responsiveness. . . . . . . 617
Kirsten M. Raehal and Laura M. Bohn
37 Agmatine: Biological Role and Therapeutic Potentials
in Morphine Analgesia and Dependence. . . . . . . . . . . . . . . . . . . . . . . . 625
Soundar Regunathan